The invention relates to clinical depression, the leading cause of medical disability in the world, and more specifically to a method for determining what antidepressant regimen is best suited for a patient with depression.
Presently, there are few guidelines for determining the appropriate agents to use in treating depressed patients. Traditional thinking holds that all antidepressants are the same except for side-effects. This assumption is based on the fact that all antidepressants show approximately the same level of effectiveness (50-70%) in studies on undifferentiated depressed populations. However, recent investigations which differentiate between subtypes of depression indicate that matching antidepressants with specific subtypes can improve results. Unfortunately, none of the depression assessment tools currently available identify these subtypes (e.g., DSM-IV-TR, Hamilton, Beck, Montgomery-Asberg, Zung). Thus, many health professionals seeing such patients fail to make the proper diagnosis and, when they attempt to treat may not always use medications optimally.
There accordingly remains a need for an improved method that permits even inexperienced providers to quickly, easily, inexpensively, and accurately determine which type of depression is present (e.g. whether the depression is primarily characterized by (1) impaired CNS modulation, with typical symptoms of anxiety, irritability, hostility, impulsivity, agitation, hypochondriasis, or suicidality; (2) impaired activation, with common symptoms of fatigue, apathy, anhedonia, hypersomnia, lack of initiative, inability to concentrate, and decreased productivity, or (3) a combination of both types) and to prescribe the treatment regimen that is most likely to lead to clinical improvement.
A half century ago the discovery that depression was often improved by medications affecting monoamine neurotransmitters led to several optimistic “one disease-one neurotransmitter” theories. The norepinephrine and serotonin hypotheses of depression posited simple synaptic deficiencies of these chemicals as the basis of depression. Advances in neuroscience and more rigorous clinical research ultimately demonstrated problems with these theories, such as delays in clinical improvement until weeks or months after correction of putative synaptic deficiencies and the comparable efficacies in undifferentiated depressed populations. By the end of the 20th century, identification of complex intraneuronal pathways involving multiple signaling systems and neuroadaptive genetic transcription mechanisms seemed to offer more compelling explanatory possibilities. Thus, most practitioners have been encouraged to believe that differences between serotonergic and catecholaminergic antidepressants are of little importance.
The concept of “targeted treatment” in depression, i.e., the use of a particular class of antidepressant against a particular depressive subtype, had until recently found little scientific support. Over a quarter century ago Klein and his co-workers showed “dirty” antidepressants such as tricyclics and monoamine oxidase inhibitors's (MAOI'S) to be somewhat more beneficial in melancholia and a typical depression, respectively. However, since 1988, with the introduction of “cleaner” agents like fluoxetine (Prozac and others), selective serotonin reuptake inhibitors (SSRI's) have demonstrated higher efficacies than catecholaminergic agents in treating many disorders such as anxiety, panic, phobias, postraumatic stress (PTSD), premenstrual disorder (PMS) and obsessive-compulsive disorder (OCD). On the other hand, catecholaminergic agents such as bupropion (Wellbutrin) and reboxetine have shown greater effectiveness in restoring energy, motivation and libido. Supporting the idea that neurotransmitter mechanisms matter, depletion experiments have shown that the condition of a successfully treated depressed patient will worsen if depleted of the neurotransmitter that his or her antidepressant treatment has targeted, but not if other neurotransmitters are depleted. Similarly, pre-treatment Q-EEG measurements can predict whether depressed patients will respond to a serotonergic as opposed to another type of antidepressant. In severe depressions, dual mechanism regimens (serotonergic and catecholaminergic) are more effective than monotherapies.
Because of the potential clinical importance of targeting, the inventor has been studying and matching selective serotonergic and catecholaminergic antidepressants to particular subtypes of depression for over a decade. The naturalistic outpatient study on which the invention is based involved 1000 depressed patients. In a random sample of 100 patients who were treated according to the invention's targeting algorithm, 96% were improved (CGI ratings <3) compared with 65% given standard non-targeted treatment (n=55). More recently, 12 patients who received the wrong treatment according to the invention exhibited only 29% as much improvement as 84 people treated according to the invention's recommendations.
Embodying the knowledge gained in these studies, the invention provides clinicians in diverse settings with a rapid, user-friendly method for selecting antidepressants that are more likely to prove effective.